This program project emphasizes the interaction of intrinsic aging processes with diseases of multifactoral origin. Although there are many such processes and diseases, several have been selected which represent striking examples of a close interrelation between an aging process related to metabolism and an age-linked "disease" and, in addition, are disorders of medical and social importance in the adult and aging population. The two major areas being investigated are: (1) age changes in metabolism of connective tissues, including cartilage and bone, and their relation to age-linked structural abnormalities, including osteoporisis and degenerative arthritis; (2) age changes in carbohydrate and lipid metabolism, related to the age-linked disorders, atherosclerosis and diabetes.